Sodium Carbonate → HCID 178502634, 화합물

HRID 897462노트

반응식

HRID 897462 반응식
[CH3:1][O:2][N:3]=[C:4]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:5]1[CH:10]=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=1.I[C:27]1[C:35]2[C:30](=[N:31][CH:32]=[N:33][C:34]=2[NH2:36])[N:29]([C@H:37]2[CH2:42][CH2:41][C@@H:40]([N:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)[CH2:39][CH2:38]2)[N:28]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[CH3:1][O:2][N:3]=[C:4]([C:5]1[CH:6]=[CH:7][C:8]([C:27]2[C:35]3[C:30](=[N:31][CH:32]=[N:33][C:34]=3[NH2:36])[N:29]([C@H:37]3[CH2:38][CH2:39][C@@H:40]([N:43]4[CH2:44][CH2:45][N:46]([CH3:49])[CH2:47][CH2:48]4)[CH2:41][CH2:42]3)[N:28]=2)=[CH:9][CH:10]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 73884415phenyl-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-methanone O-methyloximeHCID 178481014HCID 178481014, 화합물

생성물 1

HCID 178502634HCID 178502634, 화합물수율 73.9%

시약·촉매·용매 2

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

A mixture of phenyl-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-methanone O-methyloxime (intermediate AQ) (0.701 g, 0.0021 mol), cis-3-iodo-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate AC) (0.80 g, 0.0018 mol), tetrakis-(triphenylphosphine)palladium (0.125 g, 0.00011 mol) and sodium carbonate (0.48 g, 0.0045 mol) was heated in a mixture of ethylene glycol dimethyl ether (40 mL) and water (20 mL) at 80° C. for 16 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and solvents were removed under the reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (100 mL), the organic layer separated and the aqueous layer further extracted with ethyl acetate twice (70 mL each). The combined organic extracts were dried over magnesium sulfate. The solvents were evaporated under reduced pressure to leave a tan solid which was purified by flash column chromatography on silica using dichloromethane/triethylamine/methanol (96:3:1) as a mobile phase to give cis-{4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-phenyl}(phenyl)methanone O-methyloxime as a white solid (0.700 g, 0.00133 mol). Cis-{4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-phenyl}(phenyl)methanone O-methyloxime (0.201 g, 0.00039 mol) was dissolved in refluxing ethanol (17 mL) and a preheated solution of maleic acid (0.178 g, 0.0015 mol) in ethanol (8 mL) was added. The mixture was refluxed for 10 min, cooled to ambient temperature and the precipitate collected by filtration, washed with ethyl acetate and dried to give cis-{4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-phenyl}(phenyl)methanone O-methyloxime dimaleate as a white solid (0.212 g, 0.00028 mol): 1H NMR (DMSO-d6, 400 MHz) 8.26 (s, 1H), 7.74 (d, 1H), 7.66 (d, 1H), 7.51 (m, 6H), 7.33 (d, 1H), 6.14 (s, 4H), 4.85 (m, 1H), 3.91 (s, 3H) 3.1 (br, 9H), 2.71 (s, 3H), 2.33 (m, 2H), 2.07 (m, 2H), 1.74 (m, 4H);

후처리

  1. customsolvents were removed under the reduced pressure
  2. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (100 mL)
  3. customthe organic layer separated
  4. extractionthe aqueous layer further extracted with ethyl acetate twice (70 mL each)
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. customThe solvents were evaporated under reduced pressure
  7. customto leave a tan solid which
  8. customwas purified by flash column chromatography on silica

출처 및 근거

ORD 기록
ord-36589033dc604e8483444d52a64e132c
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921763B2

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